Detection of oxidative mutagens in an urban air-particulate extract: a preliminary study

The Ames assays strains TA98 and TA100 have been useful in characterizing complex mixtures from organic solvent extracts of particles from diesel-powered vehicles, ambient air, and other sources. In this paper we report preliminary experiments using TA102, a bacterial strain that detects compounds that can oxidize DNA, to characterize the mutagenicity of an ambient air sample collected in Ann Arbor, MI. Four sets of ambient air filters were collected in duplicate over a period of several days. The mutagenicities of methylene chloride extracts of these filters were compared using strains TA98, TA100 and TA102. The concentration-mutagenicity data for TA98 and TA100 were linear over the concentration range 0-200 [mu]g extract/plate. The mutagenicity of the extracts using TA102 was much lower than the other two strains and was non-linear over the concentration range tested. These results suggest that it would be difficult to use TA102 to identify the oxidative mutagens present in an ambient air particulate extract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29696/1/0000028.pd

The International Academy of Health Sciences Informatics (IAHSI): 2020 Report

Objectives: To summarize the major activities of the International Academy of Health Sciences Informatics (IAHSI) in the 2020 time period and to welcome its 2020 Class of Fellows. Method: Report from the members of the Academy's Board. Results: Due to the SARS-CoV-2 pandemic, both Plenary meetings in 2020 had to be organized as virtual meetings. Scientific discussions, focusing on mobilizing computable biomedical knowledge and on data standards and interoperability formed major parts of these meetings. A statement on the use of informatics in pandemic situations was elaborated and sent to the World Health Organization. A panel on data standards and interoperability started its work. 34 Fellows were welcomed in the 2020 Class of Fellows so that the Academy now consists of 179 members. Conclusions: There was a shift from supporting to strategic activities in the Academy's work. After having achieved organizational stability, the Academy can now focus on its strategic work and so on its main objective.S

Drinking Water with Uranium below the U.S. EPA Water Standard Causes Estrogen Receptor–Dependent Responses in Female Mice

Background: The deleterious impact of uranium on human health has been linked to its radioactive and heavy metal-chemical properties. Decades of research has defined the causal relationship between uranium mining/milling and onset of kidney and respiratory diseases 25 years later. Objective: We investigated the hypothesis that uranium, similar to other heavy metals such as cadmium, acts like estrogen. Methods: In several experiments, we exposed intact, ovariectomized, or pregnant mice to depleted uranium in drinking water [ranging from 0.5 μg/L (0.001 μM) to 28 mg/L (120 μM). Results: Mice that drank uranium-containing water exhibited estrogenic responses including selective reduction of primary follicles, increased uterine weight, greater uterine luminal epithelial cell height, accelerated vaginal opening, and persistent presence of cornified vaginal cells. Coincident treatment with the antiestrogen ICI 182,780 blocked these responses to uranium or the synthetic estrogen diethylstilbestrol. In addition, mouse dams that drank uranium-containing water delivered grossly normal pups, but they had significantly fewer primordial follicles than pups whose dams drank control tap water. Conclusions: Because of the decades of uranium mining/milling in the Colorado plateau in the Four Corners region of the American Southwest, the uranium concentration and the route of exposure used in these studies are environmentally relevant. Our data support the conclusion that uranium is an endocrine-disrupting chemical and populations exposed to environmental uranium should be followed for increased risk of fertility problems and reproductive cancers

Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells

February 17, 2011The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome[superscript 1, 2, 3, 4, 5], resulting in altered patterns of gene expression[superscript 2, 6, 7, 8, 9]. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs)[superscript 10, 11] that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iPSCs compared with embryonic stem cells, suggesting that their activation may promote the emergence of iPSCs. Supporting this, our results indicate that these lincRNAs are direct targets of key pluripotency transcription factors. Using loss-of-function and gain-of-function approaches, we found that one such lincRNA (lincRNA-RoR) modulates reprogramming, thus providing a first demonstration for critical functions of lincRNAs in the derivation of pluripotent stem cells

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Transmission of Novel Influenza A(H1N1) in Households with Post-Exposure Antiviral Prophylaxis

BACKGROUND: Despite impressive advances in our understanding of the biology of novel influenza A(H1N1) virus, little is as yet known about its transmission efficiency in close contact places such as households, schools, and workplaces. These are widely believed to be key in supporting propagating spread, and it is therefore of importance to assess the transmission levels of the virus in such settings. METHODOLOGY/PRINCIPAL FINDINGS: We estimate the transmissibility of novel influenza A(H1N1) in 47 households in the Netherlands using stochastic epidemic models. All households contained a laboratory confirmed index case, and antiviral drugs (oseltamivir) were given to both the index case and other households members within 24 hours after detection of the index case. Among the 109 household contacts there were 9 secondary infections in 7 households. The overall estimated secondary attack rate is low (0.075, 95%CI: 0.037-0.13). There is statistical evidence indicating that older persons are less susceptible to infection than younger persons (relative susceptibility of older persons: 0.11, 95%CI: 0.024-0.43. Notably, the secondary attack rate from an older to a younger person is 0.35 (95%CI: 0.14-0.61) when using an age classification of <or=12 versus >12 years, and 0.28 (95%CI: 0.12-0.50) when using an age classification of <or=18 versus >18 years. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the overall household transmission levels of novel influenza A(H1N1) in antiviral-treated households were low in the early stage of the epidemic. The relatively high rate of adult-to-child transmission indicates that control measures focused on this transmission route will be most effective in minimizing the total number of infections

A Novel Extracytoplasmic Function (ECF) Sigma Factor Regulates Virulence in Pseudomonas aeruginosa

Next to the two-component and quorum sensing systems, cell-surface signaling (CSS) has been recently identified as an important regulatory system in Pseudomonas aeruginosa. CSS systems sense signals from outside the cell and transmit them into the cytoplasm. They generally consist of a TonB-dependent outer membrane receptor, a sigma factor regulator (or anti-sigma factor) in the cytoplasmic membrane, and an extracytoplasmic function (ECF) sigma factor. Upon perception of the extracellular signal by the receptor the ECF sigma factor is activated and promotes the transcription of a specific set of gene(s). Although most P. aeruginosa CSS systems are involved in the regulation of iron uptake, we have identified a novel system involved in the regulation of virulence. This CSS system, which has been designated PUMA3, has a number of unusual characteristics. The most obvious difference is the receptor component which is considerably smaller than that of other CSS outer membrane receptors and lacks a β-barrel domain. Homology modeling of PA0674 shows that this receptor is predicted to be a bilobal protein, with an N-terminal domain that resembles the N-terminal periplasmic signaling domain of CSS receptors, and a C-terminal domain that resembles the periplasmic C-terminal domains of the TolA/TonB proteins. Furthermore, the sigma factor regulator both inhibits the function of the ECF sigma factor and is required for its activity. By microarray analysis we show that PUMA3 regulates the expression of a number of genes encoding potential virulence factors, including a two-partner secretion (TPS) system. Using zebrafish (Danio rerio) embryos as a host we have demonstrated that the P. aeruginosa PUMA3-induced strain is more virulent than the wild-type. PUMA3 represents the first CSS system dedicated to the transcriptional activation of virulence functions in a human pathogen

Family-centred interventions by primary healthcare services for Indigenous early childhood wellbeing in Australia, Canada, New Zealand and the United States: a systematic scoping review

© 2017 The Author(s).Background: Primary healthcare services in Australia, Canada, New Zealand and the United States have embraced the concept of family-centred care as a promising approach to supporting and caring for the health of young Indigenous children and their families. This scoping review assesses the quality of the evidence base and identifies the published literature on family- centred interventions for Indigenous early childhood wellbeing. Methods: Fourteen electronic databases, grey literature sources and the reference lists of Indigenous maternal and child health reviews were searched to identify relevant publications from 2000 to 2015. Studies were included if the intervention was: 1) focussed on Indigenous children aged from conception to 5 years from the abovementioned countries; 2) led by a primary healthcare service; 3) described or evaluated; and 4) scored greater than 50% against a validated scale for family-centredness. The study characteristics were extracted and quality rated. Reported aims, strategies, enablers and outcomes of family-centredcare were identified using grounded theory methods. Results: Eighteen studies (reported in 25 publications) were included. Three were randomised controlled studies; most were qualitative and exploratory in design. More than half of the publications were published from 2012 to 2015. The overarching aim of interventions was to promote healthy families. Six key strategies were to: support family behaviours and self- care, increase maternal knowledge, strengthen links with the clinic, build the Indigenous workforce, promote cultural/ community connectedness and advocate for social determinants of health. Four enablers were: competent and compassionate program deliverers, flexibility of access, continuity and integration of healthcare, and culturally supportive care. Health outcomes were reported for Indigenous children (nutritional status; emotional/behavioural; and prevention of injury and illness); parents/caregivers (depression and substance abuse; and parenting knowledge, confidence and skills); health services (satisfaction; access, utilization and cost) and community/cultural revitalisation. Discussion and conclusion: The evidence for family-centred interventions is in the early stages of development, but suggests promise for generating diverse healthcare outcomes for Indigenous children and their parents/caregivers, as well as satisfaction with and utilisation of healthcare, and community/cultural revitalisation. Further research pertaining to the role of fathers in family-centred care, and the effects and costs of interventions is needed